POS1217 ANTI-TNF THERAPY FOR IMMUNE MEDIATED INFLAMMATORY DISEASES MAY BE ASSOCIATED WITH LOWER ANTIBODY LEVELS AND VIRUS NEUTRALIZATION EFFICACY FOLLOWING SARS-CoV-2 mRNA VACCINATION
Authors: N. Finkelstein, R. M. Dayam, J. Law, R. Goetgebuer, G. Chao, K. T. Abe, M. Sutton, J. M. Stempak, D. Pereira, D. Croitoru, L. Acheampong, S. Rizwan, K. Rymaszewski, R. Milgrom, D. Ganatra, N. V. Batista, M. Girard, I. Lau, R. Law, M. Cheung, B. Rathod, J. Kitaygorodsky, R. Samson, Q. Hu, N. Haroon, R. Inman, V. Piguet, M. Silverberg, A. C. Grigras, T. H. Watts, V. Chandran
Journal: Annals of the Rheumatic Diseases (2022)

Background The impact of immunosuppressants on COVID-19 vaccination response and durability in patients with immune-mediated inflammatory diseases (IMID) is yet to be fully characterized. Humoral response may be attenuated in these patients especially those on B cell depleting therapy and higher doses of corticosteroids, but data regarding other immunosuppressants are scarce. Objectives We aimed to investigate antibody and T cell responses and durability to SARS-CoV-2 mRNA vaccines (BNT162b and/or mRNA 1273) in IMID patients on immunomodulatory maintenance therapy other than B-cell depleting therapy and corticosteroids. Methods This prospective observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with IMIDs (psoriatic arthritis, psoriasis, inflammatory bowel disease and rheumatoid arthritis) with or without maintenance immunosuppressive therapies (anti-TNF, methotrexate/azathioprine [MTX/AZA], anti-TNF + MTX/AZA, anti IL12/23, anti-IL-17, anti-IL23) compared to healthy controls. Automated ELISA for IgGs to spike trimer, spike receptor binding domain (RBD) and the nucleocapsid (NP) and T-cell release of 9 cytokines (IFNg, IL2, IL4, IL17A, TNF) and cytotoxic molecules (sFasL, GzmA, GzmB, Perforinin) in cell culture supernatants following stimulation with spike or NP peptide arrays were conducted at 4 time points: T1=pre vaccination, T2=median 26 days after dose 1, T3=median 16 days after dose 2 and T4=median 106 days after dose 2. Neutralization assays against four SARS-CoV-2 variants (wild type, delta, beta and gamma) were conducted at T3. Results We followed 150 subjects: 26 healthy controls and 124 IMID patients: 9 untreated, 44 on anti-TNF, 16 on anti-TNF with MTX/AZA, 10 on anti-IL23, 28 on anti-IL12/23, 9 on anti-IL17, 8 on MTX/AZA (Table 1). Most patients mounted antibody and T cell responses with increases from dose 1 to dose 2 (100% seroconversion at T3) and some decline by T4, with variability within groups. Antibody levels and neutralization efficacy was lower in anti-TNFgroups (anti-TNF, anti-TNF + MTX/AZA) compared to controls and waned by T4 (Figure 1). T cell responses were not consistently different between groups. Pooled data showed a higher antibody response to mRNA-1273 compared to BNT162b. Table 1. Baseline characteristics of study participants Control untreated IMID Anti- TNF Anti- TNF +MTX/AZA Anti-IL-23 Anti -IL-12/23 Anti -IL-17 MTX/AZA n=26 n=9 n=44 n=16 n=10 n=28 n=9 n=8 p-value IMID* N/A IBD 9 30 10 0 27 0 4 Psoriasis 1 3 1 8 1 2 2 PA 0 7 3 2 1 7 2 AS 0 8 3 0 0 1 0 RA 1 1 0 0 0 1 1 Age median years [IQR] 36 [26-46] 33 [27-41] 38 [30-51] 53 [44-59] 48 [45-61] 34 [28-47] 49 [46-61] 42 [31-55] &lt;0.001^ Sex male (%) 16 (62) 5 (56) 18 (41) 8 (50) 5 (50) 13 (46) 6 (67) 4 (50) 0.772~ BMI median kg/m2 [IQR] 25 [23-28] 26 [22-27] 22 [24-26] 26 [24-28] 27 [24-35] 22 [21-24] 32 [26-34] 26[25-33] 0.001^ Vaccine interval median days [IQR] 74 [35-84] 54 [31-64] 60 [45-69] 64 [50-72] 74 [35-84] 62 [49-69] 65 [52-75] 58 [21-97] 0.372^ *multiple IMIDs per patient possible Figure 1. Antibody responses (A) Anti spike and anti RBD IgG levels at indicated time points. Blue line represents median ratio in convalescent patients. The red line is the seropositivity threshold: the median antibody level of those that pass both a 1% false positive rate and show ≥3SD from the log means of the negative controls. (B) Relative ratio of RBD, spike and NP across time. Black and gray lines indicate median and mean values, respectively. *p≤0.05, **p≤0.01, ***p≤0.001, ****p≤0.0001 Conclusion Following 2 doses of mRNA vaccination there is 100% seroconversion in IMID patients on maintenance therapy. Antibody levels and neutralization efficacy in anti-TNF group are lower than controls, and wane substantially by 3 months after dose 2. These findings highlight the need for third dose in patients undergoing treatment with anti-TNF therapy and continued monitoring of immunity in these patient groups, taking into consideration newer variants and additional vaccine doses. Acknowledgements This work was funded by a donation from Juan and Stefania Speck and by grants VR-1 172711, VS1-175545, FDN-143250, GA1- 177703 and GA2- 177716, from Canadian Institutes of Health Research and COVID Immunity task force and by Sinai Health Foundation Disclosure of Interests Naomi Finkelstein: None declared, Roya M. Dayam: None declared, Jaclyn Law: None declared, Rogier Goetgebuer: None declared, Gary Chao: None declared, Kento T. Abe: None declared, Mitchell Sutton: None declared, Joanne M. Stempak: None declared, Daniel Pereira: None declared, David Croitoru: None declared, Lily Acheampong: None declared, Saima Rizwan: None declared, Klaudia Rymaszewski: None declared, Raquel Milgrom: None declared, Darshini Ganatra: None declared, Nathalia V. Batista: None declared, Melanie Girard: None declared, Irene Lau: None declared, Ryan Law: None declared, Michelle Cheung: None declared, Bhavisha Rathod: None declared, Julia Kitaygorodsky: None declared, Reuben Samson: None declared, Queenie Hu: None declared, Nigil Haroon: None declared, Robert Inman Consultant of: AbbVie, Janssen, Lilly, Novartis., Grant/research support from: AbbVie, Novartis, Vincent Piguet Consultant of: AbbVie, Almirall, Celgene, Janssen, Kyowa Kirin Co. Ltd, LEO Pharma, Novartis, Pfizer, Sanofi, UCB, and Union Therapeutic, Grant/research support from: Unrestricted educational grants from AbbVie, Bausch Health, Celgene, Janssen, LEO Pharma, Lilly, L’Oréal, NAOS, Novartis, Pfizer, Pierre-Fabre, Sandoz, and Sanofi, Mark Silverberg Speakers bureau: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Consultant of: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Grant/research support from: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Anne-Claude Grigras: None declared, Tania H. Watts: None declared, Vinod Chandran Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Eli-Lilly.